Whole-genome sequencing as a tool for studying the microevolution of drug-resistant serial Mycobacterium tuberculosis isolates

Jaciara de Lourdes do Carmo Guimarães Diniz; Andrea von Groll; Gisela Unis; Elis Regina Dalla-Costa; Maria Lúcia Rosa Rossetti; Júlia Silveira Vianna; Daniela Fernandes Ramos; Ana Júlia Reis; Priscila Cristina Bartolomeu Halicki; João Luis Rheingantz Scaini; Yasmin Castillos de Ibrahim das Neves; Jody Phelan; Ana Rita Gomes; Susana Campino; Karina dos Santos Machado; Adriano Velasque Werhli; Arnab Pain; Taane Gregory Clark; João Perdigão; Miguel Viveiros; Isabel Portugal; Pedro Eduardo Almeida Silva

doi:10.1016/j.tube.2021.102137

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Whole-genome sequencing as a tool for studying the microevolution of drug-resistant serial Mycobacterium tuberculosis isolates

Journal article

Peer reviewed

Whole-genome sequencing as a tool for studying the microevolution of drug-resistant serial Mycobacterium tuberculosis isolates

Jaciara de Lourdes do Carmo Guimarães Diniz, Andrea von Groll, Gisela Unis, Elis Regina Dalla-Costa, Maria Lúcia Rosa Rossetti, Júlia Silveira Vianna, Daniela Fernandes Ramos, Ana Júlia Reis, Priscila Cristina Bartolomeu Halicki, João Luis Rheingantz Scaini, …

Tuberculosis (Edinburgh, Scotland), Vol.131, pp.102137-102137

01/12/2021

DOI: https://doi.org/10.1016/j.tube.2021.102137

PMID: 34673379

Abstract

Catalase assay

Exogenous reinfection

Microevolution

Resistance

Whole-genome sequencing

Treatment of drug-resistant tuberculosis requires extended use of more toxic and less effective drugs and may result in retreatment cases due to failure, abandonment or disease recurrence. It is therefore important to understand the evolutionary process of drug resistance in Mycobacterium tuberculosis. We here in describe the microevolution of drug resistance in serial isolates from six previously treated patients. Drug resistance was initially investigated through phenotypic methods, followed by genotypic approaches. The use of whole-genome sequencing allowed the identification of mutations in the katG, rpsL and rpoB genes associated with drug resistance, including the detection of rare mutations in katG and mixed populations of strains. Molecular docking simulation studies of the impact of observed mutations on isoniazid binding were also performed. Whole-genome sequencing detected 266 single nucleotide polymorphisms between two isolates obtained from one patient, suggesting a case of exogenous reinfection. In conclusion, sequencing technologies can detect rare mutations related to drug resistance, identify subpopulations of resistant strains, and identify diverse populations of strains due to exogenous reinfection, thus improving tuberculosis control by guiding early implementation of appropriate clinical and therapeutic interventions.

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Title: Whole-genome sequencing as a tool for studying the microevolution of drug-resistant serial Mycobacterium tuberculosis isolates
Creators - without role: Jaciara de Lourdes do Carmo Guimarães Diniz - Núcleo de Pesquisa em Microbiologia Médica, Faculdade de Medicina, Universidade Federal do Rio Grande, Rio Grande, Rio Grande do Sul, Brazil
Andrea von Groll - Núcleo de Pesquisa em Microbiologia Médica, Faculdade de Medicina, Universidade Federal do Rio Grande, Rio Grande, Rio Grande do Sul, Brazil
Gisela Unis - Hospital Sanatório Partenon, Secretaria Estadual de Saúde do Rio Grande do Sul (HSP SES/RS), Porto Alegre, Rio Grande do Sul, Brazil
Elis Regina Dalla-Costa - Centro de Desenvolvimento Científico e Tecnológico, Porto Alegre, Rio Grande do Sul, Brazil
Maria Lúcia Rosa Rossetti - Universidade Luterana do Brasil
Júlia Silveira Vianna - Núcleo de Pesquisa em Microbiologia Médica, Faculdade de Medicina, Universidade Federal do Rio Grande, Rio Grande, Rio Grande do Sul, Brazil
Daniela Fernandes Ramos - Núcleo de Pesquisa em Microbiologia Médica, Faculdade de Medicina, Universidade Federal do Rio Grande, Rio Grande, Rio Grande do Sul, Brazil
Ana Júlia Reis - Núcleo de Pesquisa em Microbiologia Médica, Faculdade de Medicina, Universidade Federal do Rio Grande, Rio Grande, Rio Grande do Sul, Brazil
Priscila Cristina Bartolomeu Halicki - Núcleo de Pesquisa em Microbiologia Médica, Faculdade de Medicina, Universidade Federal do Rio Grande, Rio Grande, Rio Grande do Sul, Brazil
João Luis Rheingantz Scaini - Combi-Lab – Grupo de Biologia Computacional, Centro de Ciências Computacionais C3, Universidade Federal do Rio Grande, Rio Grande, Rio Grande do Sul, Brazil
Yasmin Castillos de Ibrahim das Neves - Núcleo de Pesquisa em Microbiologia Médica, Faculdade de Medicina, Universidade Federal do Rio Grande, Rio Grande, Rio Grande do Sul, Brazil
Jody Phelan - London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, United Kingdom
Ana Rita Gomes - London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, United Kingdom
Susana Campino - London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, United Kingdom
Karina dos Santos Machado - Combi-Lab – Grupo de Biologia Computacional, Centro de Ciências Computacionais C3, Universidade Federal do Rio Grande, Rio Grande, Rio Grande do Sul, Brazil
Adriano Velasque Werhli - Combi-Lab – Grupo de Biologia Computacional, Centro de Ciências Computacionais C3, Universidade Federal do Rio Grande, Rio Grande, Rio Grande do Sul, Brazil
Arnab Pain - King Abdullah University of Science and Technology
Taane Gregory Clark - London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, United Kingdom
João Perdigão - Research Institute for Medicines - iMed.ULisboa, Faculdade de Farmácia, Universidade de Lisboa, Lisboa, Portugal
Miguel Viveiros - Universidade Nova de Lisboa
Isabel Portugal - Research Institute for Medicines - iMed.ULisboa, Faculdade de Farmácia, Universidade de Lisboa, Lisboa, Portugal
Pedro Eduardo Almeida Silva - Núcleo de Pesquisa em Microbiologia Médica, Faculdade de Medicina, Universidade Federal do Rio Grande, Rio Grande, Rio Grande do Sul, Brazil
Publication Details: Tuberculosis (Edinburgh, Scotland), Vol.131, pp.102137-102137
Publisher: Elsevier Ltd
Identifiers: 9944528408331
Academic Unit: King Abdullah University of Science & Technology
Language: English
Resource Type: Journal article